Neutropenic Fever in Pediatric Cancer Patients

Introduction

What is it?

Neutropenia in the pediatric cancer patient: absolute neutrophil count (ANC) < 500 cells/microliter or ANC that is expected to decrease to <500 cells/µL in next 48 hours.

Fever: generally defined as a single oral temperature >to 38.3°C (101° F) in neutropenic patient; a temperature > 38° C (100.4° F) for one hour or two elevations; a temperature >38° C (100.4° F) during a 12-hour period are additional definitions that may be used

Rectal temperature is never to be used due to the risk of mucosal damage and associated bacteremia

Why does it matter?

Infectious complications from chemotherapy-induced myelosuppression are a major cause of morbidity and mortality in pediatric cancer patients.

Neutropenic fever is one of the most common reasons for ED visits among pediatric cancer patients.

Etiology of Fever

Febrile neutropenia may be diagnosed as fever of unknown origin in approximately 70% of patients

However, infection is documented in 10-40% of neutropenic fever patients

Gram positives often now identified as source of bacteremia, which is thought to be partially due to the increasingly frequent use of prophylactic antibiotics in pediatric patients receiving chemotherapy

Evaluation

Start with a thorough, but targeted history:

It is important to ask about site-specific symptoms, antimicrobial prophylaxis, infection exposures, chemotherapy agents used and stage of therapy (to anticipate the length of the neutropenic episode), intravascular catheters

Initial therapy with a broad-spectrum antipseudomonal beta-lactam (e.g., cefepime or ceftazidime), a carbapenem (e.g., meropenem or imipenem-cilastatin), or piperacillin-tazobactam is recommended for uncomplicated episodes of fever in neutropenic patients

Studies have demonstrated that empiric monotherapy with these agents is as efficacious as combination therapy but with fewer adverse events

If a carbapenem is to be used, meropenem is preferred due to risk of seizures with imipenem-cilastatin

Additional therapies may be needed based on clinical presentation

For example, consider addition of metronidazole for abdominal symptoms, particularly pain or blood per rectum

The 2010 Infectious Diseases Society of American (IDSA) guidelines recommend that vancomycin be reserved for the following clinical scenarios:

Hypotension or other signs of cardiopulmonary deterioration

Radiographically documented pneumonia

Clinically suspected central venous line site infection (eg, chills or rigors with infusion through the catheter and cellulitis around the catheter entry or exit site)

Skin or soft tissue infection at any site

Known colonization with MRSA, penicillin- and cephalosporin-resistant Streptococcus pneumoniae

When a blood culture has been reported to be growing gram-positive bacteria and identification and susceptibility testing are pending

Empiric antifungal therapy may be added for high-risk patients who have persistent fever after 4-7 days of broad-spectrum antibiotics and no identified source; lipid formulations of amphotericin B often used; may also consider CT of sinuses and chest, serial fungal serology

Endpoint for therapy: negative cultures after 48 hours, afebrile for at least 24 hours, and evidence of marrow recovery

Inconvenient for donors: have to get screened, receive steroids and G-CSF (these medications increase the number of granulocytes that can be collected from donor and prolong their survival) before they can donate

Donors are also at risk for mild side effects: headaches, arthralgia, bone aches, fatigue and insomnia most common